Sjöstrand Dan, Carlsson Jonas, Paratcha Gustavo, Persson Bengt, Ibáñez Carlos F
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
J Biol Chem. 2007 Apr 27;282(17):12734-40. doi: 10.1074/jbc.M701588200. Epub 2007 Feb 23.
Most plasma membrane proteins are capable of sensing multiple cell-cell and cell-ligand interactions, but the extent to which this functional versatility is founded on their modular design is less clear. We have identified the third immunoglobulin domain of the Neural Cell Adhesion Molecule (NCAM) as the necessary and sufficient determinant for its interaction with Glial Cell Line-derived Neurotrophic Factor (GDNF). Four charged contacts were identified by molecular modeling as the main contributors to binding energy. Their mutation abolished GDNF binding to NCAM but left intact the ability of NCAM to mediate cell adhesion, indicating that the two functions are genetically separable. The GDNF-NCAM interface allows complex formation with the GDNF family receptor alpha1, shedding light on the molecular architecture of a multicomponent GDNF receptor.
大多数质膜蛋白能够感知多种细胞间和细胞与配体间的相互作用，但其功能多样性在多大程度上基于其模块化设计尚不清楚。我们已确定神经细胞黏附分子（NCAM）的第三个免疫球蛋白结构域是其与胶质细胞系源性神经营养因子（GDNF）相互作用的必要且充分决定因素。通过分子建模确定了四个带电接触点是结合能的主要贡献者。它们的突变消除了GDNF与NCAM的结合，但NCAM介导细胞黏附的能力保持不变，这表明这两种功能在遗传上是可分离的。GDNF-NCAM界面允许与GDNF家族受体α1形成复合物，这为多组分GDNF受体的分子结构提供了线索。
